摘要
目的探讨人肝细胞癌(HCC)中组蛋白赖氨酸N端甲基转移酶SET结构域分支型1(SETDB1)的表达及其对肿瘤生长的影响。方法采用免疫组织化学法检测HCC组织中SETDB1的表达水平;shRNA慢病毒转染MHCC97H细胞构建SETDB1稳定敲低细胞系;平板克隆形成试验及流式细胞仪检测细胞增殖、凋亡的变化;裸鼠皮下移植瘤模型检测沉默SETDB1对肿瘤生长的影响;Western blot检测组蛋白H3K9me3表达变化。结果在HCC组织中SETDB1表达水平与正常肝组织比较有差异(P<0.05);SETDB1高表达患者肿瘤体积更大(P<0.05);下调SETDB1能抑制MHCC97H细胞增殖,促进细胞凋亡(P<0.05);下调SETDB1的表达也抑制MHCC97H细胞裸鼠皮下移植瘤的生长(P<0.05);沉默SETDB1后MHCC97H细胞内H3K9me3的表达降低(P <0.05),p53表达升高(P <0.05)。结论 SETDB1在HCC中表达升高,下调SETDB1能够通过组蛋白H3在K9位点的甲基化而发挥抗肿瘤生长作用。
Objective To investigate the expression of SETDB1 in hepatocellular carcinoma(HCC)and its role in tumor growth.Methods The expression of SETDB1 in HCC was detected by immunohistochemical staining.SETDB1 specific shRNA-lentivirus was used to knock down the expression of SETDB1 in MHCC97H cells.Clone formation assay and flow cytometry were used to detect cell proliferation and apoptosis.A subcutaneous xenotransplanted tumor model was used to measure the effect of SETDB1 on tumor growth in vivo.Western blot was used to detect the expression of H3K9me3.Results The expression of SETDB1 in the HCC tissues was higher than that in the normal liver tissues(P<0.05).The tumor volume was bigger in the patients with high SETDB1 expression(P<0.05).Down-regulation of SETDB1 suppressed proliferation and enhanced apoptosis in MHCC97H cells(P<0.05).Knockdown of SETDB1 still inhibited in vivo tumor growth in nude mice(P<0.05).Moreover,the expression of H3K9me3 in MHCC97H cells was impaired due to the depletion of SETDB1(P<0.05),but the p53 expression was up-regulated(P<0.05).Conclusions The expression of SETDB1 increases in HCC tissues.Downregulation of SETDB1 could inhibit HCC growth in vitro and in vivo through inhibiting H3K9 trimethylation.
作者
陈静
刘莉
郑思琳
Jing Chen;Li Liu;Si-lin Zheng(Department of Hepatobiliary Surgery,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646099,China)
出处
《中国现代医学杂志》
CAS
2018年第32期38-43,共6页
China Journal of Modern Medicine
作者简介
[通信作者]郑思琳,E-mail:791697074@qq.com。
